The long-term goal of the proposed research is to assess the interrelationships between biliary bile acid and cholesterol, and plasma lipoprotein cholesterol and triglyceride, with particular emphasis on hepatic metabolism as it influences the catabolism of lipoprotein cholesterol and the association of bile acids and triglyceride during fed and fasting states in the normal bile acid- and lipoprotein-depleted animals. Such interrelationships will be examined in the baboon by determining hepatic uptake, release, and/or secretion of plasma lipoproteins, clearance from the extrasplanchnic (Hepatic) region, and catabolism into bile. Furthermore, the interrelations between plasma VLDL-triglyceride w/bile acids and other lipoprotein components will be assessed. A baboon model with exteriorized but intact enterohepatic circulation and chronic multiple indwelling vascular catheters will allow the simultaneous assessment of biliary bile acid, phospholipid, and cholesterol secretion and relative composition, and bile acid turnover with that of plasma lipoprotein metabolism by transgradient analysis (transplanchnic, transportal, and transhepatic gradients) during fed vs. fasting state; intact vs. interrupted enterohepatic circulation; lipoprotein depleted (by plasmaphoresis); and cholesterol gallstones formation. Low and high density labelled cholesterol and apoprotein will be followed from plasma through liver into bile while VLDL labelled TGFA will be used to assess VLDL-triglyceride secretion and interaction with bile acids in such states. These methods will therefore allow simultaneous assessment of lipoprotein and biliary lipid interaction in a primate model whose lipid metabolism is similar to that of man. In addition, total body exchangeable cholesterol may also be evaluated in these experiments where metabolic steady-states exist.